Bourgeois Jeffrey S, Jacob Jeeva, Garewal Aram, Ndahayo Renata, Paxson Julia
Department of Biology, College of the Holy Cross, Worcester, MA, 01610, United States of America.
PLoS One. 2016 Sep 20;11(9):e0163182. doi: 10.1371/journal.pone.0163182. eCollection 2016.
Cellular exposure to cigarette smoke leads to an array of complex responses including apoptosis, cellular senescence, telomere dysfunction, cellular aging, and neoplastic transformation. To study the cellular response to cigarette smoke, a common in vitro model exposes cultured cells to a nominal concentration (i.e. initial concentration) of soluble cigarette smoke extract (CSE). However, we report that use of the nominal concentration of CSE as the only measure of cellular exposure is inadequate. Instead, we demonstrate that cellular response to CSE exposure is dependent not only on the nominal concentration of CSE, but also on specific experimental variables, including the total cell number, and the volume of CSE solution used. As found in other similar xenobiotic assays, our work suggests that the effective dose of CSE is more accurately related to the amount of bioavailable chemicals per cell. In particular, interactions of CSE components both with cells and other physical factors limit CSE bioavailability, as demonstrated by a quantifiably reduced cellular response to CSE that is first modified by such interactions. This has broad implications for the nature of cellular response to CSE exposure, and for the design of in vitro assays using CSE.
细胞暴露于香烟烟雾会引发一系列复杂反应，包括细胞凋亡、细胞衰老、端粒功能障碍、细胞老化和肿瘤转化。为了研究细胞对香烟烟雾的反应，一种常见的体外模型将培养的细胞暴露于可溶性香烟烟雾提取物（CSE）的标称浓度（即初始浓度）下。然而，我们报告称，仅使用CSE的标称浓度作为细胞暴露的唯一指标是不够的。相反，我们证明细胞对CSE暴露的反应不仅取决于CSE的标称浓度，还取决于特定的实验变量，包括细胞总数和所用CSE溶液的体积。正如在其他类似的异源生物测定中所发现的那样，我们的研究表明，CSE的有效剂量与每个细胞中生物可利用化学物质的量更准确相关。特别是，CSE成分与细胞以及其他物理因素之间的相互作用会限制CSE的生物利用度，这表现为细胞对CSE的反应因这种相互作用而首先发生可量化的降低。这对细胞对CSE暴露的反应性质以及使用CSE的体外测定设计具有广泛影响。
